Miniature Dachshund Research Articles

Adult‐onset neuronal ceroid lipofuscinosis in a smooth‐haired dachshund

AbstractA 5‐year‐old, smooth‐haired miniature dachshund exhibited a progressive history of frequent episodes of aggression towards objects, head pressing, circling and intermittent pelvic limb ataxia over a period of 2 weeks. Visual impairment was also noticed several months prior. Neurolocalisation was consistent with forebrain disease. Blood and urine analysis, magnetic resonance imaging of the brain and cerebrospinal fluid analysis were all unremarkable. The patient was euthanased due to disease progression, and postmortem histopathological analysis and electronic microscopy identified the accumulation of intracellular granular material in a number of neurons, mainly located in the thalamus and hypothalamus. This supported a diagnosis of neuronal ceroid lipofuscinosis. Genetic testing showed no mutations in the causative genes reported for this breed. This case reports the occurrence of a potentially novel subtype of neuronal ceroid lipofuscinosis, due to a currently unidentified genetic mutation, leading to an adult onset of clinical signs in the dachshund.

A unified characterization of convolution coefficients in nonlocal differential equations

In loving memory of my beloved miniature dachshund Maddie (16 March 2002 – 16 March 2020). We consider nonlocal differential equations with convolution coefficients of the form \[{-}M\Big(\big(a*(g\circ |u|)\big)(1)\Big)u''(t)=\lambda f\big(t,u(t)\big),\quad t\in(0,1), \] in the case in which $g$ can satisfy very generalized growth conditions; in addition, $M$ is allowed to be both sign-changing and vanishing. Existence of at least one positive solution to this equation equipped with boundary data is considered. We demonstrate that the nonlocal coefficient $M$ allows the forcing term $f$ to be free of almost all assumptions other than continuity.

Population genetics for 18 short tandem repeat loci (Canine GenotypesTM Panel 2.1 Kit) of 150 unrelated dogs from three pure-bred groups in Japan

Similar to that in Europe and the United States, the need for forensic DNA identification in dogs is increasing in Japan. As few studies have used commercial genotyping kits, the effectiveness of the Canine GenotypesTM Panel 2.1 Kit for individual DNA identification in dogs bred in Japan was examined. We genotyped 150 unrelated dogs (50 Golden Retrievers, 50 Miniature Dachshunds, and 50 Shiba Inu) at 18 canine short tandem repeat loci by the Kit. The allele frequency, expected heterozygosity, observed heterozygosity, p-value, power of the discriminant, and of exclusion, polymorphic information content, and random matching probability were calculated for each marker. The random matching probability was subsequently estimated to be 4.394×10-22 in the 150 dogs of the three pure-bred groups based on 18 STR loci; 3.257 × 10−16 in the Golden Retriever, 3.933 × 10−18 in the Miniature Dachshund, and 2.107 × 10−18 in the Shiba Inu breeds. In addition, principal component analysis based on genotype data revealed the Golden Retrievers, Miniature Dachshunds, and Shiba Inus separated into three clusters. The results of the genotype analysis showed that the Canine GenotypesTM Panel 2.1 Kit could be useful for identity testing and tool of population study of canines in Japan.

Vulvar oedema secondary to exogenous oestrogen exposure in a paediatric canine patient

AbstractA 12‐week‐old, female, entire miniature dachshund presented with a 3‐week history of progressive vulval enlargement with an associated clear serous sanguinolent discharge. Vulval oedema was noted on clinical exam. Further investigations included a complete cell count, computer tomography and a guarded vaginal swab, which revealed vaginal epithelial cell keratinisation. After thorough anamnesis, the clinical signs were concluded to be a result of exogenous oestrogen exposure.

Treatment of an Infrabony Defect of a Maxillary Canine Tooth Using Enamel Matrix Derivatives with Allogeneic Bone Augmentation in a Dog.

A 5-year-old Miniature Dachshund was presented having an infrabony pocket on the palatal aspect of the right maxillary canine tooth. The bony defect had worsened despite previous closed root planing and administration of a perioceutic agent. A second surgery using an allogeneic cancellous bone augmentation with an enamel matrix derivative was performed in the infrabony defect following open root planing. Eight months after the periodontal surgery, the osseous defect showed healing by improved periodontal probing measurements and increased radiopacity using dental radiography and computed tomography.

Factors related to longevity and mortality of dogs in Italy

Besides its translational value, an improved understanding of dog longevity and mortality is necessary to guide health management decisions, breed selection, and improve dog welfare. In order to analyse the lifespan of dogs in Italy, identify the most common causes of death, and evaluate possible risk factors, anonymised medical records were collected from 9 veterinary teaching hospitals and 2 public health institutions. Data regarding breed, sex, neuter status, age, diagnosis, and mechanism of death were retrieved. Cause of death (COD) was classified by pathophysiologic process (PP) and organ system (OS). Of the 4957 dogs that died between 2004 and 2020 included in the study, 2920 (59.0%) were purebred, 2293 (46.2%) were female, 3005 (60.6%) were intact, 2883 (58.2%) were euthanised. Overall median longevity was 10.0 years. Median longevity was significantly longer for crossbreds, females, neutered dogs, and small-sized breeds. The breeds with the highest median age at death were the Yorkshire terrier, English cocker spaniel, West Highland white terrier, Italian volpino, and Shih Tzu, whilst the American bulldog, English bulldog, American pit bull terrier, Bernese mountain dog and the Maremma and the Abruzzes sheepdog had the lowest median age at death. The most frequent COD by PP was neoplasia (34.0%), which occurred more frequently in large breeds, namely German shepherd, Labrador retriever and Boxer. Degenerative diseases mostly affected small-sized dogs like Miniature pinscher and Dachshund. Regarding the OS involved, diseases of the renal/urinary system were most frequently responsible for COD (15.0%), prevalently degenerative and inflammatory/infectious. Substantial variation in median longevity according to causes of death by PP and OS was observed. These data are relevant for breeders, veterinary practitioners, and owners, to assist breed selection, facilitate early diagnosis, guide choice when purchasing a purebred dog and making health management decisions, and ultimately improve dog welfare.

Transcriptomic analysis of bone marrow specimens collected from Miniature Dachshunds diagnosed with non-neoplastic bone marrow disorders.

Non-neoplastic bone marrow disorders are main causes of non-regenerative anemia in dogs. Despite the high incidence of the diseases, their molecular pathophysiology has not been elucidated. We previously reported that Miniature Dachshund (MD) was a predisposed breed to be diagnosed with non-neoplastic bone marrow disorders in Japan, and immunosuppressive treatment-resistant MDs showed higher number of platelets and morphological abnormalities in peripheral blood cells. These data implied that treatment-resistant MDs might possess distinct pathophysiological features from treatment-responsive MDs. Therefore, we conducted transcriptomic analysis of bone marrow specimens to investigate the pathophysiology of treatment-resistant MDs. Transcriptomic analysis comparing treatment-resistant MDs and healthy control dogs identified 179 differentially expressed genes (DEGs). Pathway analysis using these DEGs showed that "Wnt signaling pathway" was a significantly enriched pathway. We further examined the expression levels of DEGs associated with Wnt signaling pathway and confirmed the upregulation of AXIN2 and CCND2 and the downregulation of SFRP2 in treatment-resistant MDs compared with treatment-responsive MDs and healthy control dogs. This alteration implied the activation of Wnt signaling pathway in treatment-resistant MDs. The activation of Wnt signaling pathway has been reported in human patients with myelodysplastic syndrome (MDS), which is characterized by dysplastic features of blood cells. Therefore, the results of this study implied that treatment-resistant MDs have distinct molecular pathological features from treatment-responsive MDs and the pathophysiology of treatment-resistant MDs might be similar to that of human MDS patients.

Activation of the Wnt/β-catenin signaling pathway and CTNNB1 mutations in canine intestinal epithelial proliferative lesions.

Nuclear expression of β-catenin has been reported in canine intestinal epithelial tumors (IETs) and colorectal inflammatory polyps (CIPs) with dysplastic epithelia. However, the role of the Wnt/β-catenin signaling pathway in these lesions remains unclear. To investigate the association between the nuclear β-catenin expression and the activation of the Wnt/β-catenin signaling pathway, immunohistochemistry and mutation analyses were conducted on 64 IETs and 20 CIPs. IETs and CIPs with β-catenin nuclear and/or cytoplasm immunolabeling were classified as β-catenin (+). The immunostaining scores of c-Myc and Cyclin D1 and Ki-67 index were significantly higher in β-catenin (+) cases than in β-catenin (-) cases. Identical APC mutations (p.E154D and p.K155X) were detected in 6/41 β-catenin (+) IETs; all 6 of IETs with APC mutations were Jack Russell Terriers. CTNNB1 mutations were detected in 29/42 β-catenin (+) IETs, 3/11 β-catenin (+) CIPs, and 2/22 β-catenin (-) IETs, most of which were hotspots associated with human colorectal carcinoma. In one Miniature Dachshund diagnosed with a CIP that subsequently developed into an IET, the same CTNNB1 mutation was detected in both lesions. The immunohistochemical results suggest that cell proliferative activity in β-catenin (+) cases may be associated with activation of the Wnt/β-catenin signaling pathway. The mutation analysis results suggest that CTNNB1 mutations may be associated with cytoplasmic β-catenin accumulation in IET and CIP. Furthermore, the dysplastic epithelium in CIP may progress to IET through the activation of the Wnt/β-catenin signaling pathway by the CTNNB1 mutation.

Reverse sneezing, unilateral epistaxis, and acute-onset seizures in a 9-year-old spayed female miniature Dachshund.

Reverse sneezing, unilateral epistaxis, and acute-onset seizures in a 9-year-old spayed female miniature Dachshund.

Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients.

Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal disease characterized by the presence of idiopathic chronic inflammation, in Miniature Dachshund (MD) and found 31 missense disease-associated SNPs by whole-exome sequencing. We sequenced them in 10 other dog breeds and found five, PLG, TCOF1, TG, COL9A2 and COL4A4, only in MD. We then investigated two rare and breed-specific missense SNPs (T/T SNPs), PLG: c.477G > T and c.478A>T, and found that ICRPs with the T/T SNP risk alleles showed less intact plasminogen and plasmin activity in the lesions compared to ICRPs without the risk alleles but no differences in serum. Moreover, we show that MMP9, which is an NF-κB target, caused the plasminogen reduction and that intestinal epithelial cells expressing plasminogen molecules were co-localized with epithelial cells expressing MMP9 in normal colons with the risk alleles. Importantly, MMP9 expression in patients with ulcerous colitis or Crohn's disease also co-localized with epithelial cells showing enhanced NF-κB activation and less plasminogen expression. Overall, our zoobiquity experiments showed that MMP9 induces the plasminogen reduction in the intestine, contributing to the development of local inflammation and suggesting the local MMP9-plasminogen axis is a therapeutic target in both dogs and patients. Therefore, zoobiquity-type experiments could bring new perspectives for biomarkers and therapeutic targets.

Preemptively planned en bloc resection of an extensive right adrenal pheochromocytoma involving the right hepatic division, caval thrombus and segmental caudal vena cava in a dog with Budd−Chiari‐like syndrome

Surgical resection is the treatment of choice for canine adrenal pheochromocytomas (PHEOs). Information on en bloc resection of adrenal PHEO with tumour thrombus, right hepatic division and segmental caudal vena cava (CVC) running through the adrenal tumour and right hepatic division is limited. To describe the preemptively planned en bloc resection of an extensive right adrenal PHEO involving the right hepatic division, the caval thrombus and the segmental CVC in a dog with Budd-Chiari-like syndrome (BCLS). A 13-year-old castrated male miniature dachshund was referred for surgical treatment due to anorexia, lethargy and severe abdominal distension caused by abundant ascites. Preoperative computed tomography (CT) revealed a large mass in the right adrenal gland with a large caval thrombus obstructing the CVC and hepatic veins, which caused BCLS. Additionally, collateral vessels were formed between the CVC and azygos veins. No findings suggested obvious metastases. Based on CT findings, an en bloc resection of the adrenal tumour with caval thrombus, right hepatic division and segmental CVC was planned. The preoperatively planned resection was feasible; the tumour was completely resected grossly. The operation time and total Pringle manoeuvre time were 162min and 16min 56 s, respectively. There was no postoperative hindlimb oedema, renal dysfunction, ascites or abdominal distention. The patient's clinical signs, including appetite, fully improved. Hospitalization lasted 16 days. However, the patient died on the 130th postoperative day due to suspected metastases and cachexia. Even in case of an extensive infiltration of adrenal PHEO causing BCLS, an en bloc resection might be successfully achieved based on the preoperative CT findings speculating the collateral vessels formed for caudal venous return.

Trismus due to myotonia associated with hyperadrenocorticism in a dog.

We present the report of trismus due to hyperadrenocorticism-associated myotonia diagnosed by electromyography in a dog. An intact female Miniature Dachshund, 13 years and 9 months old, presented with stiff gait and trismus as well as polyuria and polydipsia. Abdominal ultrasonography showed enlarged adrenal glands. An adrenocorticotropic hormone stimulation test revealed an exaggerated response. Based on these findings, this case was diagnosed with hyperadrenocorticism. Electromyography revealed myotonic discharge in the temporalis muscle and limbs. Therefore, trismus was considered to be caused by hyperadrenocorticism-associated myotonia, and the case was treated with oral trilostane (1.3 mg/kg, once daily). During the 4-month follow-up period, despite the partial improvement in stiff gait, trismus did not recover. Long-term data on more cases are warranted to assess the prognosis and clinical characteristics of trismus due to hyperadrenocorticism-associated myotonia.

Effects of age, sex, and breed on the composition of free extractable ceramides in the stratum corneum of healthy dogs.

Ceramide (CER), an important component of the extracellular lamellar lipids in the stratum corneum (SC), plays a critical role in maintaining the cutaneous barrier function. This study aimed to determine whether the quantity of free extractable SC CERs in dogs was affected by the age, sex, or breed. Fifty-eight dogs from the breeds Shiba Inu, beagle, miniature dachshund, shih tzu, and golden retriever, without any history of skin problems, were enrolled in this study. Lipid extracts from the SC were subjected to high-performance thin-layer chromatography to quantify the free extractable CERs. There were weak negative correlations between the age and the amount of free extractable CERs, CER [NP] (non-hydroxy fatty acids linked to phytosphingosines), CER [AS/NH] (α-hydroxy fatty acids linked to sphingosines/non-hydroxy fatty acids linked to 6-hydroxysphingosines), and CER [AP] (α-hydroxy fatty acids and phytosphingosines). There were no significant sex- or breed-related differences in the amounts of free extractable SC CERs in the dogs. These findings imply that aging causes a decline in the amount of free extractable SC CERs in dogs, similar to that observed in humans. The sex or breed of the dogs investigated in this study did not influence the amount of free extractable SC CERs.

MYO5A Frameshift Variant in a Miniature Dachshund with Coat Color Dilution and Neurological Defects Resembling Human Griscelli Syndrome Type 1.

A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the clinical signs, histopathological changes and underlying genetic defect. The puppy had visible coat color dilution and was unable to hold its head on its own or to remain in a stable prone position for an extended period. Histopathological examination revealed an accumulation of clumped melanin and deposition of accumulated keratin within the hair follicles, accompanied by dermal pigmentary incontinence. These dermatological changes were compatible with the histopathology described in dogs with an MLPH-related dilute coat color. We sequenced the genome of the affected dog and compared the data to 795 control genomes. MYO5A, coding for myosin VA, was investigated as the top functional candidate gene. This search revealed a private homozygous frameshift variant in MYO5A, XM_022412522.1:c.4973_4974insA, predicted to truncate 269 amino acids (13.8%) of the wild type myosin VA protein, XP_022268230.1:p.(Asn1658Lysfs*28). The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 142 additionally genotyped, unrelated Dachshund dogs. MYO5A loss of function variants cause Griscelli type 1 syndrome in humans, lavender foal in horses and the phenotype of the dilute mouse mutant. Based on the available data, together with current knowledge on other species, we propose the identified MYO5A frameshift insertion as a candidate causative variant for the observed dermatological and neurological signs in the investigated dog.

Gene expression profile of peripheral blood mononuclear cells in mild to moderate obesity in dogs

BackgroundMolecular mechanisms and early diagnosis on the development of mild to moderate of canine obesity are not understood although recent dog obesity is a widespread problem. To understand the differences between normal weight and mild to moderate obesity, the purpose of this study is to investigate the gene expression profiles of peripheral blood mononuclear cells (PBMC) in dogs. MethodsThis study comprised a sample of 12 privately-owned Miniature Dachshund, which were divided into two groups (obese and control) based on body condition scores (BCS). Serum biochemical parameters and PBMC gene expression profiles were compared between groups. ResultsA statistically significant between group differences was recorded for body weight (BW), BCS, serum Insulin and triglyceride (TG) levels (p < 0.05). RNA-seq revealed the upregulated 154 genes and the downregulated 198 genes in obese dogs at more than 3.5-fold change compared with control animals. Hemoglobin subunits alpha- and beta-like were detected in the downregulated genes. RT-PCR analysis showed downregulation of FOLH1, ALAS2 and LOC100855540 genes, and upregulation of BCL2L15 gene, suggesting that the metabolic difference between normal and mild to moderate obesity was involved in the hemoglobin metabolism. ConclusionsThis study revealed significant differences in the gene expression of BCL2L15, FOLH1, ALAS2, and hemoglobin subunits such as LOC100855540 between normal weight and mild to moderate obese dogs, which indicate that these genes may prevent the obesity in dogs and be potentially useful for diagnosis of mild to moderate obesity.

Dog leukocyte antigen (DLA) class II genotypes associated with chronic enteropathy in French bulldogs and miniature dachshunds

Canine chronic enteropathy (CE) is a group of immunogenetic disorders of unclear etiology characterized by chronic or recurrent gastrointestinal signs and inflammation. Diagnosis of CE subtypes by treatment response is a lengthy and challenging process, particularly in refractory cases of the disease. Given known association of dog leukocyte antigen (DLA) class II genotype and various immunogenetic disorders between and across breeds, this study was designed to examine the potential of determining susceptibility to refractory CE through identification of risk and protective genotypes in French bulldogs and miniature dachshunds—two popular dog breeds in Japan.Sequence-based genotyping of three DLA class II genes in 29 French bulldogs and 30 miniature dachshunds with refractory CE revealed a protective haplotype DLA-DRB1*002:01-DQA1*009:01-DQB1*001:01 against CE in French bulldogs (OR 0.09, 95 % CI 0.01−0.71, p = 0.0084). No statistical difference was noted between miniature dachshund cases and controls. These findings, largely disparate from a previous study on German shepherd dogs in the UK, were taken as possible indication of etiological differences in the refractory CE noted between and within breeds, and by extension, the potential of identifying such disease heterogeneity by DLA typing.The DLA-DQA1/DQB1 haplotype, protective against CE in our French bulldogs, has been reported as protective in various immune-mediated disorders such as Doberman hepatitis (Dyggve et al., 2011). Likewise, the DLA-DRB1*006:01 risk allele for Doberman hepatitis was noted in more French bulldogs with CE compared to controls, in line with reports on genotypes associated with both risk and protection being shared across various autoimmune diseases and breeds.These findings support an immunogenetic basis to the French bulldog-CE in our analysis, calling for further DLA studies working with larger samples and different breeds towards phenotypic clarification that may aid in early diagnosis, treatment, and prophylaxis through epigenetic approaches and breeding.

Myocardial Fibrosis with Cartilaginous Tissue Formation in Right Atrial Auricle of a Dog

A 13-year-old castrated male Miniature Dachshund exhibited oedema of the face and cervical region. Clinical examination, including computed tomography, revealed a mass on the right atrial wall. Histopathological examination of the mass revealed proliferation of spindle cells, which formed intersecting bundles and abundant proteoglycan material. Multiple islands of hyaline cartilage were also observed within foci of proliferated spindle cells. Although the proliferated spindle cells replaced the myocardial parenchyma, there was no evidence of malignancy. The spindle cells were immunopositive for vimentin and α-smooth muscle actin, while chondrocytes were immunopositive for vimentin and S100. Neither the spindle cells nor the chondrocytes were immunolabelled for cytokeratin AE1/AE3, desmin, factor VIII, melan A, p63 or Ki-67. These findings indicate that the lesion represented myocardial fibrosis with cartilaginous tissue formation.

Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D

BackgroundA cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified.MethodsMuscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.ResultsMuscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents.ConclusionsThis first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

Clinical and clinicopathological features and outcomes of Miniature Dachshunds with bone marrow disorders.

Non-neoplastic bone marrow disorders such as non-regenerative immune-mediated anemia, pure red cell aplasia, and myelodysplastic syndrome are major causes of non-regenerative anemia in dogs. However, there has been no study on the clinical and clinicopathological features of canine non-neoplastic bone marrow disorders in Japan. Hence, we first investigated the breed disposition of non-neoplastic bone marrow disorders that induce anemia as a retrospective study and found that Miniature Dachshund (MD) was a predisposed breed. Based on this finding, we investigated the clinical and clinicopathological features of non-neoplastic bone marrow disorders in MDs as a preliminary retrospective study, and we compared them between immunosuppressive treatment-responsive and -resistant MDs. We found that treatment-resistant MDs showed thrombocytosis and increased frequencies of dysplastic features in the peripheral blood. These results indicate that bone marrow disorders in treatment-resistant MDs might manifest distinct features compared with those in treatment-sensitive MDs, and sensitivity to immunosuppressive treatments could be predicted based on thrombocytosis and dysplastic features in the peripheral blood. Further studies that examine aberrations in the genome are needed to elucidate the pathophysiology of bone marrow disorders in MDs.

Association analysis of non-synonymous polymorphisms of interleukin-4 receptor-α and interleukin-13 genes in canine atopic dermatitis.

Interleukin-4 (IL4) and interleukin-13 (IL13) are involved in the initial response of T helper 2 lymphocytes through the activation of the IL4 receptor alpha (IL4RA), which is a common receptor chain for these cytokines. In humans, several single-nucleotide polymorphisms (SNPs) identified in the IL4R and in interleukin coding genes were associated with atopic disorders. However, the association between canine IL4R polymorphisms and atopic disorders has not been investigated yet. This study aimed to determine the associations between four non-synonymous SNPs and canine atopic dermatitis (CAD) in shiba inu and miniature dachshund populations. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis were used to genotype four polymorphisms of canine IL4R and IL13 in 34 shiba inu and 19 miniature dachshund patients with CAD, as well as 29 shiba inu and 39 miniature dachshund patients without the condition. Results from miniature dachshunds revealed a potential association between the presence of minor A allele rs24378020 and CAD (odds ratio, 0.10; 95% confidence interval, 0.01–0.85; Poriginal=0.0062). This CAD resistance allele led to an amino acid substitution (Arg688Cys) that could impair IL4 and IL13 signaling. In shiba inu patients, rs24378020 was fixed by homozygosity of the major G allele. No association was found between the remaining three evaluated SNPs and CAD. Nevertheless, the study suggests that the IL4R Cys688 variant reduces the risk of CAD in miniature dachshunds.